Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
22,496
result(s) for
"Harris, David"
Sort by:
Aβ receptors specifically recognize molecular features displayed by fibril ends and neurotoxic oligomers
Several cell-surface receptors for neurotoxic forms of amyloid-β (Aβ) have been described, but their molecular interactions with Aβ assemblies and their relative contributions to mediating Alzheimer’s disease pathology have remained uncertain. Here, we used super-resolution microscopy to directly visualize Aβ-receptor interactions at the nanometer scale. We report that one documented Aβ receptor, PrP
C
, specifically inhibits the polymerization of Aβ fibrils by binding to the rapidly growing end of each fibril, thereby blocking polarized elongation at that end. PrP
C
binds neurotoxic oligomers and protofibrils in a similar fashion, suggesting that it may recognize a common, end-specific, structural motif on all of these assemblies. Finally, two other Aβ receptors, FcγRIIb and LilrB2, affect Aβ fibril growth in a manner similar to PrP
C
. Our results suggest that receptors may trap Aβ oligomers and protofibrils on the neuronal surface by binding to a common molecular determinant on these assemblies, thereby initiating a neurotoxic signal.
PrP
C
, a receptor for Aβ oligomers, blocks polarized elongation of Aβ fibrils by binding to the rapidly growing end of each fibril. PrP
C
and other receptors may trap Aβ oligomers and protofibrils on the neuronal surface by binding to a common molecular determinant, initiating a neurotoxic signal.
Journal Article
Inferring species interactions from co-occurrence data with Markov networks
Inferring species interactions from co-occurrence data is one of the most controversial tasks in community ecology. One difficulty is that a single pairwise interaction can ripple through an ecological network and produce surprising indirect consequences. For example, the negative correlation between two competing species can be reversed in the presence of a third species that outcompetes both of them. Here, I apply models from statistical physics, called Markov networks or Markov random fields, that can predict the direct and indirect consequences of any possible species interaction matrix. Interactions in these models can be estimated from observed co-occurrence rates via maximum likelihood, controlling for indirect effects. Using simulated landscapes with known interactions, I evaluated Markov networks and six existing approaches. Markov networks consistently outperformed the other methods, correctly isolating direct interactions between species pairs even when indirect interactions or abiotic factors largely overpowered them. Two computationally efficient approximations, which controlled for indirect effects with partial correlations or generalized linear models, also performed well. Null models showed no evidence of being able to control for indirect effects, and reliably yielded incorrect inferences when such effects were present.
Journal Article
Effects of Allopurinol on the Progression of Chronic Kidney Disease
This randomized trial assessed whether urate-lowering treatment with allopurinol could attenuate eGFR decline in at-risk patients with stage 3 or 4 chronic kidney disease. Allopurinol did not slow the decline in eGFR as compared with placebo.
Journal Article
Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 and is spread person-to-person through close contact. We aimed to investigate the effects of physical distance, face masks, and eye protection on virus transmission in health-care and non-health-care (eg, community) settings.
We did a systematic review and meta-analysis to investigate the optimum distance for avoiding person-to-person virus transmission and to assess the use of face masks and eye protection to prevent transmission of viruses. We obtained data for SARS-CoV-2 and the betacoronaviruses that cause severe acute respiratory syndrome, and Middle East respiratory syndrome from 21 standard WHO-specific and COVID-19-specific sources. We searched these data sources from database inception to May 3, 2020, with no restriction by language, for comparative studies and for contextual factors of acceptability, feasibility, resource use, and equity. We screened records, extracted data, and assessed risk of bias in duplicate. We did frequentist and Bayesian meta-analyses and random-effects meta-regressions. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. This study is registered with PROSPERO, CRD42020177047.
Our search identified 172 observational studies across 16 countries and six continents, with no randomised controlled trials and 44 relevant comparative studies in health-care and non-health-care settings (n=25 697 patients). Transmission of viruses was lower with physical distancing of 1 m or more, compared with a distance of less than 1 m (n=10 736, pooled adjusted odds ratio [aOR] 0·18, 95% CI 0·09 to 0·38; risk difference [RD] −10·2%, 95% CI −11·5 to −7·5; moderate certainty); protection was increased as distance was lengthened (change in relative risk [RR] 2·02 per m; pinteraction=0·041; moderate certainty). Face mask use could result in a large reduction in risk of infection (n=2647; aOR 0·15, 95% CI 0·07 to 0·34, RD −14·3%, −15·9 to −10·7; low certainty), with stronger associations with N95 or similar respirators compared with disposable surgical masks or similar (eg, reusable 12–16-layer cotton masks; pinteraction=0·090; posterior probability >95%, low certainty). Eye protection also was associated with less infection (n=3713; aOR 0·22, 95% CI 0·12 to 0·39, RD −10·6%, 95% CI −12·5 to −7·7; low certainty). Unadjusted studies and subgroup and sensitivity analyses showed similar findings.
The findings of this systematic review and meta-analysis support physical distancing of 1 m or more and provide quantitative estimates for models and contact tracing to inform policy. Optimum use of face masks, respirators, and eye protection in public and health-care settings should be informed by these findings and contextual factors. Robust randomised trials are needed to better inform the evidence for these interventions, but this systematic appraisal of currently best available evidence might inform interim guidance.
World Health Organization.
Journal Article
Development and validation of a simulation workload measure: the simulation task load index (SIM-TLX)
Virtual reality (VR) simulation offers significant potential for human factors training as it provides a novel approach which enables training in environments that are otherwise dangerous, impractical or expensive to simulate. While VR training has been adopted in many environments, such as heavy industry, surgery and aviation, there remains an inadequate understanding of how virtual simulations impact cognitive factors. One such factor, which needs careful consideration during the design of VR simulations, is the degree of mental or cognitive load experienced during training. This study aimed to validate a newly developed measure of workload, based on existing instruments (e.g. the NASA-TLX), but tailored to the specific demands placed on users of simulated environments. While participants completed a VR puzzle game, a series of experimental manipulations of workload were used to assess the sensitivity of the new instrument. The manipulations affected the questionnaire subscales (mental demands; physical demands; temporal demands; frustration; task complexity; situational stress; distraction; perceptual strain; task control; presence) as predicted in all cases (ps < .05), except for presence, which displayed little relationship with other aspects of task load. The scale was also found to have good convergent validity with an alternate index of task load. The findings support the sensitivity of the new instrument for assessing task load in virtual reality. Overall, this study contributes to the understanding of mental workload in simulated environments and provides a practical tool for use in both future research and applications in the field.
Journal Article